A. Know the function of the circulation, identify component parts.

B. Understand hemodynamic principles as they apply to health and disease.  The relationships between pressure (P), resistance (R) and flow (Q) are of primary importance.

C.Identify the contributions of the components circulation to the acute regulation of pressure, resistance, and flow.

A. Continuous flow.
B. Variable amount.
C. Variable distribution.
D. What we are describing is TRANSPORT which is achieved via:

1. Circulation of blood in a closed system of vessels and
2. Exchange of materials between blood and extravascular tissues.

A. The Heart maintains the continuous flow required in IA.  The heart is a dual pump system feeding 2 circulations:

1. Systemic Circulation: characterized by high P and high R. The characteristics of the Systemic Circulation are the primary subject of this lecture.
2. Pulmonary Circulation : (a focus of my lecture on Special Circulations) is characterized by low P and low R.  It should be obvious that you will be expected to compare and contrast the circulations of the pulmonary and systemic circuits)
3. C.O. Right heart = C.O. Left heart
4. Equal ejectates from the two pumps also means that the inputs must be equal. Adult human stroke volume per pump is 80 ml and thus cardiac output of 5600 ml/min is injected into each circuit.

Questions:  What heart rate will give at CO of 5.6 L/min ?
If stroke volume does not change and heart rate increases to 112beats per minute (bpm), what CO will be achieved?
As occurs in heavy exercise filling time decreases and reduces stroke volume.  Calculate CO for a heart rate of 175 bpm and your calculated stroke volume; compare this to the CO achieved at 175 bpm when stroke volume is 45 ml.

5. One-way system.

FIGURE 1. Vessels of the systemic circulation showing relative sizes and structures

B. Vessels (Fig. 1) are conduits, resistance elements, and barriers to exchange

1. Wall construction depends on specific vessel function.  Basic elements are:

a. Endothelial cells line the entire circulatory system, form a barrier to exchange, are involved intimately in modulation of vascular smooth muscle function, and produce and process vasoactive agents.
b. Vascular smooth muscle is the contractile element that allows vessel diameter to be a variable thus allowing IB and IC to be achieved.
c. Elastin fibers provide elasticity and energy conservation.
d. Collagen fibers provide strength and resistance to stretch.

2. Histology: all vessels except venules and capillaries consist of 3 layers:

a. Intima = endothelial cell layer.
b. Media = vascular smooth muscle and elastin.
c. Adventitia = connective tissue primarily collagen.

3. Vessel Type and Summary of Structural and Functional Features

a. Windkessels (or conduit vessels e.g. the aorta, carotids, and large arteries): involved in energy conservation and blood distribution.
b. Resistance vessels: (small arteries and arterioles) blood flow control and pre-capillary resistance.
c. Feed/Terminal arterioles control the number of perfused capillaries.
d. Capillaries are the site of solute and water exchange, diffusion, and ultrafiltration.
e. Capacitance vessels: (Venules and veins) provide post-capillary resistance, capacitance and the collection of blood for return to the heart.
f. Shunts (arteriovenous, AV, anastomoses) provide a direct pathway from arteries to veins bypassing exchange vessels.
g. Lymphatics

i. Terminal lymphatics: lymph collection from the interstitium.
ii. Lymph nodes: involved in filtration, white cell sequestration and possibly in protein concentration.
iii. Large lymph vessels: involved in conducting lymph to the great veins, fluid return to the circulation.

A. Physics of Blood Flow

1. "Ohm's Law" Analogy: The pressure gradient ( DP) provides the force to overcome the resistance (R) to flow (Q): Q = DP/R

Volume flow, Q (volume per time; ml/min), equals perfusion pressure (or effective pressure gradient,  DP (mmHg)) divided by the resistance to flow, R (mmHg min/ml).  You will see this relationship in the lung where airway ventilation replaces blood flow; you saw this relationship in Physics where you had Ohm’s Law: V = iR; I = V/R: here the voltage drop divided by resistance gives you a flow of electrons (current).

2. Volume flow describes the blood supply to an organ:

Q = vA = vpr² e.g. blood flow equals mean blood flow velocity (v, distance per time; cm/sec) per cross sectional area (A, circular surface area = pr²; cm² where r is vessel radius; cm).  Two types of flow are encountered:
a. Laminar flow represents the majority of normal blood flow.  The velocity profile is parabolic meaning that blood in the center of the vessel flows faster than blood near the vessel wall.  The mean linear velocity of blood in laminar flow is given as: v =  DPr²/(8hl) where 8 is a geometrical constant, h ("eta")is viscosity, and l the path length.
b. Turbulent flow is characterized as chaotic and the velocity profile is flattened.  Considerable stress is put on the vessel walls where turbulence occurs and on the formed elements flowing in blood.

Question: Why would laminar flow conditions facilitate exchange?
 While turbulence may accentuate mixing, why might it promote formation of thrombi or emboli?

3. Law of Continuity of Flow (Fig. 2): Blood flow in vessels of different sizes is constant in each segment of a given cross-sectional area regardless of the magnitude of that area.  If vessels run side by side  (parallel), the flow will be additive.  When one vessels lead one directly into another (series), what flows in is what flows out:

Q_total = Q₁ + Q₂ = (v₁A₁) + (v₂A₂) = Q_in = Q_out

One consequence of the Law is that with equal volume flow in successive segments (series), the linear flow velocity in each segment is inversely proportional to the cross sectional area of the segment.  Further, since radius is directly proportional to cross sectional area, centerline flow velocity is inversely proportional to the radius.  Thus, the larger the area of a single tube, the slower the flow.

When a vessel divides into two daughter vessels the total cross-sectional surface area of the daughters exceed that of the parent vessel.  The flow also divides into the daughters.  The total cross-sectional surface area of the "ideal" human aorta is about 2.5 cm²; the total cross-sectional surface area of the capillaries is 3000 cm².  The total volume flow through both places (5000 ml/min) is the same.  The flow in each capillary, though, is very, very, very small (~0.00005 ml/min).  Further, for these conditions to be true, the linear blood flow velocity in the capillaries must be much, much lower than the flow velocity in the aorta.  As will be seen in the discussion of capillary exchange:

Slow blood flow + Large surface area  =  Excellent  exchange

B. Pressures in the vascular system, arterial pressure, P_a, and venous pressure, P_v, are the forces per unit area exerted by blood on the vessel wall.

Blood pressure is

1. the force exerted by the blood against any unit area of vessel wall.
2. measured relative to atmospheric pressure.

C. Resistance: is calculated from the pressure difference between any two points in the vascular system and the volume flow.

Resistance may be seen as the ratio of the driving force (DP) to the volume flow (Q) and reflects the degree of hindrance to the flow of blood through a vessel.

1. Poiseuille’s Law defines, for laminar flow, the resistance of a viscous fluid:

Resistance is related linearly to vessel length, l, and to blood viscosity, h  ("eta"). Resistance is inversely related to vessel size (the radius to the fourth power).  Of these factors vessel radius is the most important.  Because arteries possess the capacity to alter radius to a greater extent than veins, they are considered to make up the resistance portion of the vasculature.  As a result, most of the resistance to blood flow lies upstream from the capillaries (pre-capillary resistance).

 
D. Conductance is the inverse of resistance and proportional to the fourth power of the vessel radius. Thus, an increase in vascular conductance results from a decrease in vascular resistance as would occur in the arterioles from an increase in vessel radius (dilatation).

Question:  Nitroglycerin and sodium nitroprusside are NO donors that induce vascular smooth muscle dilatation.  Why is angina relieved by nitroglycerin? (hint it is not a result of just dilating coronary arteries, despite that generally held belief)

IV. Distribution of Driving Forces: Pressure Gradients (Fig. 3)

Figure 3. Blood Pressure distribution across the systemic circulation beginning at the point where blood leaves the left ventricle and finishing at the right atrium. The solid aqua line represents the normal pressure drop across the systemic circulation.  In panel A, the dashed red line represents the pressure drop following a constriction of the arterioles and no other hemodynamic changes; in panel B the relationship is illustrated by the dashed blue line after arteriolar dilatation.

A. Normal: Blood flows through large vessels with little energy loss, e.g. without much decrease in pressure.  With each level of subdivision, vessel diameters decrease, resistance increases, energy is lost and the pressure gradient becomes steeper.  The greatest drop (75-80%) occurs across the arterioles.

B. Vasoconstriction: With arterial constriction (decrease r, increased R {Poiseuille}) arterial pressure will increase proximal (upstream) from the point of constriction (between the arterioles and the heart) and decrease distal (downstream) to the point of constriction (Fig 3A).
Thus arterial constriction is one mechanism for raising arterial blood pressure.

C. Vasodilatation: converse of the last case; increase r, decrease R, pressure decrease above the point of dilation and increase below the point of dilation (Fig. 3B).

D. Mean Filling Pressure (MFP)

1. Measures the state of filling of the vasculature.  By definition it is the pressure of the entire vasculature in the absence of cardiac activity (6-7 mmHg).  After transfusion the MFP rises transiently to 30-40 mmHg; during congestive heart failure it may rise chronically to 25 mmHg.
2. Inflow influence on outflow. MFP influences blood flow into the heart via the ventricular filling pressure.  MFP is a direct function of venous return and is consequently influenced by vascular compliance (or capacitance) and circulating blood volume.  Since MFP determines inflow of blood into the right heart it indirectly influences blood ejected by the left heart.

A. Variation with vessel type: Aorta, large arteries and relatively long arterial branches account for 19% of the total resistance to blood flow.  Terminal arteries and arterioles contribute the most, 47%.  Thus, 66% of the resistance to blood flow resides upstream of the capillaries.

B. Total Peripheral Resistance (TPR) is the overall resistance of the systemic circulation.  TPR and total volume flow (Cardiac Output, CO) determine mean systemic blood pressure (MBP which is approximately (~) equal to mean arterial pressure (MAP)) at a given moment.

MAP ~ MBP = CO * TPR = (l/min) * (mmHg min/l)

Figure 4. Vascular capacity and Cross-sectional area in this figure represents the sum of these variables for all of the vessel segments of this classification, e.g. for 1 aorta and 1 vena cava, but for 100s of large arteries and veins, thousands of small arteries and veins and millions of capillaries.  Flow velocity and pressure represent the average of those parameters in individual segments.

A. Total Blood Volume is a determinant of cardiac filling pressure during diastole; thus of the amount of blood ejected by the heart.

B. Distribution:  Of a total blood volume of 5 liters, 440 ml resides in the lungs, 4200 ml in the systemic vasculature, and 360 ml in the heart during systole.  Thus 84% of the total volume resides in the systemic vessels.

1. Systemic resistance vessel volume is 3% of total blood volume, thus, changes in arterial vessel diameter produce next to no change in blood volume distribution.
2. Capillary vessel volume is 6% of the total, thus, while capillaries are many in number and represent a huge surface area, they contain little blood.
3. Venous volume: From B1 and B2 it should be apparent that most of the blood in circulation resides in the venous system.  64% of blood volume is in the low pressure (venous) side of the circulation.  The venous circulation serves a blood storage function and changes in vessel size will redistribute blood volume.

A. Resistance vessels: characterized by high resistance and low volume.
B. Capacitance vessels: characterized by low resistance and large volume.
C. Small arteries: where small changes in dimension have marked outcome on resistance and thus pressure.
D. Small veins: where as small changes in dimension produce large changes in capacitance.
E. Pressure/Volume relationships.

A. Flow in the arterial system (Figure 4)

1. Pulsatile
2. Discontinuous: especially in the region of the aorta.
3. Energy damping. As a consequence of the artery structure, with circular elastic fibers, the vessels stretch on application of pressure and then contract back on the blood bolus serving to damp the flow and the pressure pulse.
4. Continuous and non-pulsatile in exchange vessels. By the time blood reaches the smallest vessels, the pulse pressure wave is gone: optimum conditions for exchange are achieved.

B. Pressure in the arterial system (Figure 5)

1. Arterial Pressure Pulse: Two limbs: ascending limb with a rapid rise in pressure occurring during ventricular systole and a descending limb. Characteristics include:

a. Dichrotic notch: Results from closing of aortic valve at the end of ejection during isovolemic relaxation phase of diastole.  2 pulses = di-chrotic.
b. Systolic pressure: Peak pressure, P_s
c. Diastolic pressure:  the pressure at the end of the diastolic wave,  P_d.

2. Pulse Pressure: Difference between the systolic and diastolic pressures, P_p = P_s - P_d

3. Mean Arterial Pressure (MAP):  The integrated pressure over the cycle. In practice MAP is approximated from measures of P_s and P_d by the formula:

MAP = P_d + [(P_s - P_d)/3]

MAP depends on 1) arterial blood volume and 2) elastic properties of the arterial wall.  Arterial volume, in turn, depends on the rate of blood inflow from the heart (CO) and the rate of outflow of blood from the arteries into the capillaries (Qo).  If CO exceeds Qo, arterial volume increases, the vessel walls stretch more, P rises (the ascending limb of the Fig. 5).  As outflow from the artery exceeds inflow from the heart, the walls contract back, P drops (the descending limb of Fig. 5).

A. Flow (Fig. 3):

1. Continuous with no pulse of arterial origin unless the resistance vessels are greatly dilated.
2. Pressure fluctuations show up in the main branches of the veins due to transmission of an arterial pressure pulse when anatomically veins and arteries lie side-by-side.  Pronounced fluctuations appear in the great veins nearing the right heart.  These are a result of respiratory movements and from the movement of the heart with contraction.
3. Mean flow velocity rises again leaving the capillaries in the venules and veins as the cross-sectional area is reduced.  The total area of veins is greater than that for arteries at the same branching order: thus velocity of blood in the veins is less than in the arteries.

B. Pressures:  drop sharply from 15-20 mmHg near the capillaries to 12-15 mmHg in small veins.  The next drop is to 5-6 mmHg in the large extra-thoracic veins.  The lowest pressure is at the point where veins open into the right atrium.  Where the inferior vena cava passes into the diaphragm the resistance to flow increased (caudal to the diaphragm P = 10 mmHg); at the point of transit through the diaphragm there is a step decrease in P to 4-5 mmHg.

1. Central Venous Pressure (CVP): Right atrial pressure = 2-4 mmHg and fluctuates with respiration and heart beat.
2. Venous Return: is determined from venous volume and resistance to flow.  Normally venous return is a critical determinant of stroke volume.

C. Elements influencing venous return:

1. Gravity: Increased gravitational force will result in decreased venous return; decreased SV. This is the reason for the high g-suits to keep pilots from passing out - think about the design features of these suits.
2. Hydrostatic forces:  Given what you now know about pressure gradients and flow, what will happen to venous return if Pv is higher or lower than normal.  Will venous return be influenced by changes in Pa?  Why not?
3. Exercise: see the next section
4. Thermal stress: How does heat influence vascular smooth muscle?  what will this do to vascular tone - what will this do to resistance in the arterial system; in the venous system?  Given these changes what would you predict would happen to the distribution of blood volume and venous return?

D. Mechanisms Aiding Venous Return (Figure 6)

1. Muscle pump:  Contracted skeletal muscles compress the veins.  Deep veins lie within skeletal muscles, thus on muscles contraction they tend to collapse and squeeze the veins, "pumping" blood out of the area.
2. Respiratory pump:  On inspiration pressure inside the thorax (intrathoracic) is increased tending to dilate the intrathoracic vessels (especially the relatively thin walled veins).  The venous dilatation is accompanied by a decreased resistance to flow, effectively "sucking" on blood in adjacent vessels.  This process is most effective on the superior vena cava.

Diaphragm depression on inspiration increases intra-abdominal pressure, in turn the vessel lumen is decreased, thereby decreasing abdominal vessel capacity.  The steeper pressure gradient (increased driving force) between the intra-abdominal and intrathoracic veins enhances venous inflow into the thorax.  Retrograde flow on expiration is prevented by venous valves in the limb.

Where Q = flow (volume/time) and R = resistance

 Resistors in series are additive:

Resistances in parallel are the inverse of the sum of the inverses:

 Cardiac Output = the sum of the blood flow through each organ;
 Pre load = postcapillary resistance and after load = precapillary resistance.

Questions or comments about this lecture?
If you have comments or suggestions, email me at HuxleyV@health.missouri.edu